tbuckley/cabot-search huggingface dataset:
Porto-sinusoidal vascular disorder
Authors: Andrea De Gottardi, Christine Sempoux, Annalisa Berzigotti
Journal: Journal of Hepatology (2022)

It is well established that portal hypertension can occur in the absence of cirrhosis, as reported in patients with immune disorders, infections and thrombophilia. However, similar histological abnormalities primarily affecting the hepatic sinusoidal and (peri)portal vasculature have also been observed in patients without portal hypertension. Thus, the term porto-sinusoidal vascular disorder (PSVD) has recently been introduced to describe a group of vascular diseases of the liver featuring lesions encompassing the portal venules and sinusoids, irrespective of the presence/absence of portal hypertension. Liver biopsy is fundamental for PSVD diagnosis. Specific histology findings include nodular regenerative hyperplasia, obliterative portal venopathy/portal vein stenosis and incomplete septal fibrosis/cirrhosis. Since other conditions including alcohol-related and non-alcoholic fatty liver disease, or viral hepatitis, or the presence of portal vein thrombosis may occur in patients with PSVD, their relative contribution to liver damage should be carefully assessed. In addition to histology and clinical diagnostic criteria, imaging and non-invasive tests such as liver and spleen stiffness measurements could aid in the diagnostic workup. The introduction of PSVD as a novel clinical entity will facilitate collaborative studies and investigations into the underlying molecular pathomechanisms encompassed by this term.
MEDB-40. RUNNING FOR INCLUSION IN SIOPE PNET5 MB
Authors: Maura Massimino, Luna Boschetti, Simone Minasi, Alessandra Erbetta, Luisa Chiapparini, Angela Mastronuzzi, Evelina Miele, Salvina Barra, Giovanni Scarzello, Claudia Cavatorta, Manila Antonelli, Lorenza Gandola, Francesca Romana Buttarelli
Journal: Neuro-Oncology (2022)

Abstract Enrolling medulloblastoma(MB) patients in the PNET5 protocol is a daily problem in Italy; since June 2015, 59 cases have been enrolled in 13 centres. So far, 44 of the 103 patients claiming for eligibility did not enter the protocol: 13 metastases, 5 for residual, 20 having exclusion criteria, 4 insufficient frozen material, 2 failure to comply with the correct procedures. No case was lost due to delayed centralization, which is respected even with committing weekends; review of the radiation plan was performed on Saturday for 2 cases, and radiotherapy began on the same day. We made some procedural changes to meet expected deadlines; each local centre notifies the national coordinator of a possible case's existence at MRI diagnosis, of the expected surgery date as well as its realization. MRI imaging is reviewed within 2 days after centralization. Paediatricians notify the national coordinator and pathology/biology reference centre of the MB diagnosis; the shipment of frozen tissue, blood and FFPE is booked. A slot is reserved to priority perform the central pathology review, as well as central molecular diagnosis of genetically defined subgroup (WHO classification) upon receipt of the frozen material. Upon receipt of the FFPE and frozen material, the national reference centre undertakes a double-check with the national coordinator and the local treatment centre to validate the eligibility. Within the 7th day from the receipt of the material: IHC, MYC/MYCN, Monosomy 6, beta-catenin mutation and methylation array are performed. Priority execution of somatic (blood control) sequencing of the PTCH, SUFU, and TP53 genes is also triggered for SHH-activated MB, with the deadline on the 15th day. So far we have had 99% agreement between molecular subgrouping and methylation array. CONCLUSIONS: PNET5 requirements are multiple and changing over time; difficulties may and must be overcome by mutual fast collaboration.
Nonopioid Treatments for Chronic Pain—Integrating Multimodal Biopsychosocial Approaches to Pain Management
Authors: Stephanie A. Eucker, Mitchell R. Knisely, Corey Simon
Journal: JAMA Network Open (2022)

Jason E. Goldstick, PhD; Gery P. Guy, PhD, MPH; Jan L. Losby, PhD, MSW; Grant T. Baldwin, PhD, MPH; Matthew G. Myers, MPH; Amy S. B. Bohnert, PhD
Assessing baseline cancer demographics versus those that participate in cancer clinical trials over one year in Louisiana.
Authors: Aliyah Pierre, Tara Castellano, Amelia Jernigan, Andrew G Chapple, Tingting Li, Yong Yi
Journal: Journal of Clinical Oncology (2022)

e18546 Background: To determine which barriers exist for cancer clinical trial participation in Louisiana and define areas for improvement, we report cancer demographics of all new cancer diagnoses in Louisiana in 2019 and compare those to the baseline demographics of cancer patients that enrolled on a cancer treatment trial. Methods: A retrospective study evaluating baseline cancer demographics over 2019 was performed. Our baseline population included all new cancer diagnoses in patients 18+ registered with the Louisiana Tumor Registry (LTR) between January-December 2019. Baseline demographics were compared between all patients enrolled in a cancer treatment clinical trial in 2019 through the Gulf South Clinical Trials Network (GSCTN) versus those who were not. Summary statistics were performed with regards to basic cancer and patient demographics. Results: Although patients of the highest socioeconomic group made up, n = 5,444, (21.9%) of total cancers, a larger proportion, n = 35 (32.4%), p = 0.01 ultimately enrolled in a trial. Similarly, of those living in an urban area, n = 22,258 (84.5%), a larger proportion, n = 103 (92.8%), enrolled in a trial when compared to those that were not, p = 0.02. There was a significant positive correlation (p = 0.01) between clinical trial enrollment and residency in geographic areas with higher rate of high-school graduation. Our data also demonstrated that a smaller proportion, n = 7 (6.3%), of clinical trial participants died compared to those who did not participate, n = 5176 (19.6%), p &lt; 0.01. Urologic cancer, including both prostate and bladder cancer, was the second most-diagnosed cancer primary site in Louisiana in 2019 with, n = 5481, patients diagnosed. Although black men made up, n = 1767 (32.2%) of diagnosed urologic cancer, only, n = 9 (14.1%), were accrued to participate in a urologic cancer clinical trial, p &lt; 0.01. White men, who made up, n = 3661 (66.8%), of diagnosed urologic cancer, had a larger proportion, n = 55 (85%), of trial participation, p &lt; 0.01. Conclusions: Overall, lack of geographic access proves to be a barrier for recruitment in clinical cancer trials. Patients of higher SES that live in urban areas make up a larger proportion of clinical trial participants and have better survival rates than those who do not participate. For specific cancers such as urologic cancer, further investigation on the cancer-specific inclusion and exclusion criteria must be investigated to determine the effect on equitable trial entry for populations in need. In conclusion, Louisiana offers a diverse cancer population, however, further efforts must be made to improve clinical trial access to our diverse and underserved populations.
Prognostic implications of HER2Neu-low in metastatic breast cancer.
Authors: Shaakir Hasan, Zachary Neubauer, Robert H. Press, Arpit Chhabra, Jana Lauren Fox, Oren Cahlon, Richard Lorne Bakst, Charles B. Simone, J. Isabelle Choi
Journal: Journal of Clinical Oncology (2022)

1044 Background: HER2-Low (or HER2-equivocal, FISH negative) breast cancer has historically been treated as HER2-negative; however, recent evidence suggests that there may be prognostic and/or predictive differences between the two. We explore demographic characteristics and clinical outcomes of HER2-negative and HER2-low metastatic breast cancer (MBC) patients using real world data. Methods: We queried the National Cancer Database to identify MBC patients that were HER2 0, HER2 1+, or HER2 2+ per immunohistochemical staining, with the latter two defined as HER2-low and the former HER2-negative. A multivariable binomial regression analysis identified demographic and clinical correlates of each subtype. A Cox multivariable regression analysis (MVA), propensity matched to HER2 status, was performed to identify correlates of survival. Results: After excluding missing data, 24,636 MBC patients diagnosed between 2008-2015 were identified, 6,865 (27.9%) of whom were HER2-negative and 17,771(72.1%) of whom were HER2-low. There were no differences between the two groups with respect to age, race, year treated, location, income, insurance status, Charles Deyo comorbidity score, laterality, T stage, N stage, or use of systemic therapy. HER2-low tumors were half as likely to have concomitant hormone receptor-negative status (OR = 0.49, 95% CI 0.46-0.53). The 3-year survival rate among hormone receptor-negative patients was 33.8% for HER2-low and 32.2% for HER2-negative, and 60.9% and 55.6% in HER2-low and HER2-negative cases among hormone receptor-positive patients, respectively. HER2-low cases were associated with better survival on MVA (HR = 0.91, 95% CI 0.87-0.95), and remained superior with propensity-matching (HR = 0.92, 95% CI 0.89-0.96). In a subset analysis isolated to hormone receptor-positive cases, HER2-low remained correlated with improved survival (HR = 0.93, 95% CI 0.89-0.98) with propensity-matched MVA. Correlates of worse survival include older age as a continuous variable (HR = 1.02), Black race (HR = 1.13), uninsured (HR = 1.18), comorbidity score &gt; 0 (HR = 1.28), higher T stage (HR = 1.17 to 2.34), node positivity (HR = 1.17) and, as the most influential, hormone receptor-negative status (HR = 1.94) [all P &lt; 0.01]. Conclusions: Consistent with recent data in non-MBC, our study demonstrates a small but statistically significant association with improved survival for HER2-low tumors compared to HER2-negative tumors in MBC. Randomized data are necessary to further validate this discrepancy and determine if different management is warranted for each subtype.
LGG-49. Subependymal giant cell astrocytoma associated with a cortical tuber: A case report
Authors: Valerie Anne Quinot, Karl Rössler, Martha Feucht, Gregor Kasprian, Ellen Gelpi, Christine Haberler
Journal: Neuro-Oncology (2022)

Abstract Subependymal giant cell astrocytomas (SEGAs) are circumscribed gliomas strongly associated with tuberous sclerosis (TS). TS, a rare genetic disorder caused by inactivating mutations in either of the TSC genes (TSC1/2), leads to upregulation of the mTOR pathway and consecutive cell growth. CNS manifestations other than SEGAs include cortical tubers, white matter glioneuronal hamartomas and subependymal nodules (SENs), which, although regarded as distinct morphological phenotypes, share certain histological characteristics including ballooned astrocytes and giant ganglion-like cells. SEGAs, thought to develop from the median ganglionic eminence (MGE), are most commonly located periventricularly. However, rare cases of extraventricular SEGAs have been reported. We report a case of a cortico-subcortically located SEGA in a TS patient. A two-month-old female TS patient with multiple cortical tubers presented with treatment-resistant epilepsy. A 4cm sized tuber located in the right temporal lobe, showing a transmantle sign on MRI but no typical imaging appearance of SEGA, was surgically resected. Histological evaluation revealed typical morphological characteristics of a tuber with dysmorphic neurons, balloon cells and calcifications in the cortex and adjacent white matter. Focally, a cortico-subcortically located, well delineated area with increased cellularity and morphological features of a SEGA was found. Single mitotic figures were detectable. Immunhistochemically, these cells were strongly positive for GFAP, vimentin, and nestin. Scattered S100-, NeuN-, MAP2- and SMI32-positive cells were present. No expression of class-III-b-tubulin and TTF1a was found. pS6 was expressed in a small fraction of cells. CD34 showed a dense capillary network within the lesion. This case is consistent with prior case reports of SEGA-tissue in tubers of TS patients. However, the SEGA tissue of this case did not display TTF1a-expression, characteristic for SEGAs and considered as a marker for cells originating from the MGE, thus implying a different cellular lineage.
Implication of caveolae in the pathophysiology of human acute myocardial infarction: a histological study
Authors: C Rios Navarro, G Cantos-Amores, M Ortega, J Gavara, V Marcos-Garces, E De Dios, N Perez-Sole, FJ Chorro, V Bodi, A Ruiz-Sauri
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work has been funded by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (Exp. PI20/00637) as well as by “Generalitat Valenciana” (Exp. PROMETEO/2021/008). Introduction Caveolae are lipid invaginations present in the membrane of most mammalian cells. They are mainly made up of three proteins: caveolin (Cav)-1, 2, and 3 and are involved in signal transduction and ion channels. Since caveolae regulate different signalling pathways to promote cardiac protection, the aim of this study is to compare the expression of Cav-1, 2, and 3 in the human myocardium of control subjects and in patients with myocardial infarction (MI). Materials Myocardial samples from human autopsies of 4 controls and 4 MI patients with more than 6 months of evolution were isolated. The infarction and control area were identified by haematoxylin-eosin and Masson’s trichromic stainings. The presence of Cav-1, 2 and 3 was detected by immunochemistry. Afterwards, 5 photographs were taken for each antibody and sample and the presence of each protein was morphometrically quantified using the image analyzer Image-Pro Plus. These results were also corroborated by immunofluorescence. Results A constitutive presence of Cav-1, 2, and 3 was observed in the myocardium of control patients, being Cav-1 and 3 higher expressed than Cav-2. Cav-2 and 3 were mainly found in cardiomyocytes, while Cav-1 was detected not only in cardiac muscle cells but also in endothelial cells. Comparing caveolae expression between the peri-infarct region of MI patients and controls, a significant reduction in the expression of the three proteins was observed by immunochemistry. Indeed, the decrease in Cav-2 and 3 could be also detected by immunofluorescence. Lastly, Cav-1 was more expressed in cardiomyocytes than in endothelial cells, but unlike muscle cells, its expression was not diminished after MI. Conclusions The presence of caveolin decreases in the myocardial tissue after MI. Further studies are needed to confirm the cardioprotective role of caveolae post-AMI and their use as potential therapeutic target.
The 2021 EULAR/American College of Rheumatology Points to Consider for Diagnosis, Management and Monitoring of the Interleukin‐1 Mediated Autoinflammatory Diseases: Cryopyrin‐Associated Periodic Syndromes, Tumour Necrosis Factor Receptor‐Associated Periodic Syndrome, Mevalonate Kinase Deficiency, and Deficiency of the Interleukin‐1 Receptor Antagonist
Authors: Micol Romano, Z. Serap Arici, David Piskin, Sara Alehashemi, Daniel Aletaha, Karyl Barron, Susanne Benseler, Roberta A. Berard, Lori Broderick, Fatma Dedeoglu, Michelle Diebold, Karen Durrant, Polly Ferguson, Dirk Foell, Jonathan S. Hausmann, Olcay Y. Jones, Daniel Kastner, Helen J. Lachmann, Ronald M. Laxer, Dorelia Rivera, Nicolino Ruperto, Anna Simon, Marinka Twilt, Joost Frenkel, Hal M. Hoffman, Adriana A. de Jesus, Jasmin B. Kuemmerle‐Deschner, Seza Ozen, Marco Gattorno, Raphaela Goldbach‐Mansky, Erkan Demirkaya
Journal: Arthritis & Rheumatology (2022)

Background The interleukin‐1 (IL‐1) mediated systemic autoinflammatory diseases, including the cryopyrin‐ associated periodic syndromes (CAPS), tumour necrosis factor receptor‐associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD) and deficiency of the IL‐1 receptor antagonist (DIRA), belong to a group of rare immunodysregulatory diseases that primarily present in early childhood with variable multiorgan involvement. When untreated, patients with severe clinical phenotypes have a poor prognosis, and diagnosis and management of these patients can be challenging. However, approved treatments targeting the proinflammatory cytokine IL‐1 have been life changing and have significantly improved patient outcomes. Objective To establish evidence‐based recommendations for diagnosis, treatment and monitoring of patients with IL‐1 mediated autoinflammatory diseases to standardise their management. Methods A multinational, multidisciplinary task force consisting of physician experts, including rheumatologists, patients or caregivers and allied healthcare professionals, was established. Evidence synthesis, including systematic literature review and expert consensus (Delphi) via surveys, was conducted. Consensus methodology was used to formulate and vote on statements to guide optimal patient care. Results The task force devised five overarching principles, 14 statements related to diagnosis, 10 on therapy, and nine focused on long‐term monitoring that were evidence and/or consensus‐based for patients with IL‐1 mediated diseases. An outline was developed for disease‐specific monitoring of inflammation‐induced organ damage progression and reported treatments of CAPS, TRAPS, MKD and DIRA. Conclusion The 2021 EULAR/American College of Rheumatology points to consider represent state‐of‐the‐art knowledge based on published data and expert opinion to guide diagnostic evaluation, treatment and monitoring of patients with CAPS, TRAPS, MKD and DIRA, and to standardise and improve care, quality of life and disease outcomes.
Patient-reported disruptions to cancer care in the U.S. during the COVID-19 pandemic: A national cross-sectional study.
Authors: Sharanya Iyer, Jacob Lang, Aparna Narendrula, Kristine M. Zanotti, Puneet Sindhwani, Elias Mossialos, Obi Ekwenna
Journal: Journal of Clinical Oncology (2022)

10561 Background: Disruptions to cancer care during the COVID-19 pandemic due to disease mitigation efforts, supply-chain issues, and fear of COVID-19 have all been reported, but study of their extent has been limited. The purpose of this study is to evaluate the extent and associations with patient reported disruptions to cancer treatment and other care during the COVID-19 pandemic using nationally representative data. Methods: This cross-sectional study uses data from the 2020 National Health Interview Survey (NHIS), an annual, cross-sectional survey of US adults. Adults who reported requiring current cancer treatment or other care related to their cancer in the second half of 2020 were included. Rates of patients with self-reported changes, delays, or cancellations to cancer treatment or other cancer-related care due to the COVID-19 pandemic were calculated and their associations with demographic and other variables were analyzed. All data were adjusted using sample weights and specific variables to account for stratification and other survey characteristics using the Stata svy command. Chi-square testing was used to compare proportions across variable groups. Univariable logistic regression analysis was utilized to assess variable associations with change, delay, or cancellations to cancer care during the COVID-19 pandemic. Multivariable logistic regression analysis was used to create a model adjusted for select demographic variables. Results: A sample-weighted 2,867,326 adults (n=574) reported requiring cancer treatment and/or other cancer care since the start of the COVID-19 pandemic. Of these, 189 (32.1%) reported any change, delay, or cancellation due to the pandemic. On univariable analysis, patients who were younger, female, had comorbidities, and uninsured were significantly more likely to report care disruptions. On adjusted analysis, younger age and female sex remained significant predictors. In a sample-weighted subset of 1,600,587 patients (n=331), 291 (87.9%) reported virtual appointment use. There was no association with disruptions across breast, prostate, lung, and colorectal cancer groups. Conclusions: Approximately 1/3 of patients experienced disruptions to cancer care during the COVID-19 pandemic. Patients with younger age or female sex were more likely to have disruptions in care, which may reflect risk stratification strategies in the early stages of the pandemic. The longitudinal impact of these disruptions on outcomes merits further study. [Table: see text]
Prospective Studies Comparing Structured vs Nonstructured Diagnostic Protocol Evaluations Among Patients With Fever of Unknown Origin
Authors: William F. Wright, Joshua F. Betz, Paul G. Auwaerter
Journal: JAMA Network Open (2022)

Patients meeting the criteria for fever of unknown origin (FUO) can be evaluated with structured or nonstructured approaches, but the optimal diagnostic method is unresolved.To analyze differences in diagnostic outcomes among patients undergoing structured or nonstructured diagnostic methods applied to prospective clinical studies.PubMed, Embase, Scopus, and Web of Science databases with librarian-generated query strings for FUO, PUO, fever or pyrexia of unknown origin, clinical trial, and prospective studies identified from January 1, 1997, to March 31, 2021.Prospective studies meeting any adult FUO definition were included. Articles were excluded if patients did not precisely fit any existing adult FUO definition or studies were not classified as prospective.Abstracted data included years of publication and study period, country, setting (eg, university vs community hospital), defining criteria and category outcome, structured or nonstructured diagnostic protocol evaluation, sex, temperature threshold and measurement, duration of fever and hospitalization before final diagnoses, and contribution of potential diagnostic clues, biochemical and immunological serologic studies, microbiology cultures, histologic analysis, and imaging studies. Structured protocols compared with nonstructured diagnostic methods were analyzed using regression models.Overall diagnostic yield was the primary outcome.Among the 19 prospective trials with 2627 unique patients included in the analysis (range of patient ages, 10-94 years; 21.0%-55.3% female), diagnoses among FUO series varied across and within World Health Organization (WHO) geographic regions. Use of a structured diagnostic protocol was not significantly associated with higher odds of yielding a diagnosis compared with nonstructured protocols in aggregate (odds ratio [OR], 0.98; 95% CI, 0.65-1.49) or between Western Europe (Belgium, France, the Netherlands, and Spain) (OR, 0.95; 95% CI, 0.49-1.86) and Eastern Europe (Turkey and Romania) (OR, 0.83; 95% CI, 0.41-1.69). Despite the limited number of studies in some regions, analyses based on the 6 WHO geographic areas found differences in the diagnostic yield. Western European studies had the lowest percentage of achieving a diagnosis. Southeast Asia led with infections at 49.0%. Noninfectious inflammatory conditions were most prevalent in the Western Pacific region (34.0%), whereas the Eastern Mediterranean region had the highest proportion of oncologic explanations (24.0%).In this systematic review and meta-analysis, diagnostic yield varied among WHO regions. Available evidence from prospective studies did not support that structured diagnostic protocols had a significantly better rate of achieving a diagnosis than nonstructured protocols. Clinicians worldwide should incorporate geographical disease prevalence in their evaluation of patients with FUO.